Resistant Hypertension: Disease Burden and Emerging Treatment Options

Abstract

Purpose of Review To define resistant hypertension (RHT), review its pathophysiology and disease burden, identify barriers to effective hypertension management, and to highlight emerging treatment options. Recent Findings RHT is defined as uncontrolled blood pressure (BP) ≥ 130/80 mm Hg despite concurrent prescription of ≥ 3 or ≥ 4 antihypertensive drugs in different classes or controlled BP despite prescription of ≥ to 4 drugs, at maximally tolerated doses, including a diuretic. BP is regulated by a complex interplay between the renin–angiotensin–aldosterone system, the sympathetic nervous system, the endothelin system, natriuretic peptides, the arterial vasculature, and the immune system; disruption of any of these can increase BP. RHT is disproportionately manifest in African Americans, older patients, and those with diabetes and/or chronic kidney disease (CKD). Amongst drug-treated hypertensives, only one-quarter have been treated intensively enough (prescribed > 2 drugs) to be considered for this diagnosis. New treatment strategies aimed at novel therapeutic targets include inhibition of sodium-glucose cotransporter 2, aminopeptidase A, aldosterone synthesis, phosphodiesterase 5, xanthine oxidase, and dopamine beta-hydroxylase, as well as soluble guanylate cyclase stimulation, nonsteroidal mineralocorticoid receptor antagonism, and dual endothelin receptor antagonism. Summary The burden of RHT remains high. Better use of currently approved therapies and integrating emerging therapies are welcome additions to the therapeutic armamentarium for addressing needs in high-risk aTRH patients.

Genetic Variation in ABCB1, ADRB1, CYP3A4, CYP3A5, NEDD4L and NR3C2 Confers Differential Susceptibility to Resistant Hypertension among South Africans

“…RHTN is characterized by poor response to antihypertensive medication and is a relevant outcome of interest in pharmacogenomic research. RHTN is defined as either a blood pressure (BP) that remains above target (≥140/90 mmHg) while taking more than three antihypertensive drugs including a diuretic or a controlled BP (<140/90 mmHg) while taking four or more antihypertensive drugs in adherent patients [5].…”